- Volume 15 Issue 17
DOI QR Code
A Novel Mutant of Human Papillomavirus Type 18 E6E7 Fusion Gene and its Transforming Activity
- Zhou, Zhi-Xiang (College of Life Science and Bioengineering, Beijing University of Technology) ;
- Zhao, Chen (College of Life Science and Bioengineering, Beijing University of Technology) ;
- Li, Qian-Qian (College of Life Science and Bioengineering, Beijing University of Technology) ;
- Zeng, Yi (College of Life Science and Bioengineering, Beijing University of Technology)
- Published : 2014.09.15
Background: Persistent human papillomavirus (HPV) infection, especially with high-risk types such as HPV16 and HPV18, has been identified as the primary cause of cervical cancer. E6 and E7 are the major onco-proteins of high-risk HPVs, which are consistently expressed in HPV infected tissues but absent in normal tissues and represent ideal therapeutic targets for immunotherapy of cervical cancer. Materials and Methods: In this study, the optimized fusion gene HPV18 E6E7 (HPV18 ofE6E7) was constructed according to genetic codon usage for human genes. At the same time, for safety future clinical application, a mutant of HPV18 ofE6E7 fusion gene was generated by site-directed mutagenesis at L52G for the E6 protein and C98G for the E7 protein. Results: HPV18-E6E7 mutant (HPV18 ofmE6E7) constructed in this work not only lost the transformation capability for NIH 3T3 cells and tumorigenicity in BALB/c nude mice, but also maintained very good stability and antigenicity. Conclusion: These results suggest that the mutant should undergo further study for application as a safe antigenspecific therapeutic vaccine for HPV18-associated tumors.
- Balsitis S, Dick F, Dyson N, et al (2006). Critical roles for nonpRb targets of human papillomavirus type 16 E7 in cervical carcinogenesis. Cancer Res, 66, 9393-400. https://doi.org/10.1158/0008-5472.CAN-06-0984
- Cannon G, Gupta P, Gomes F, et al (2012). Prevention of cancer and non-communicable diseases. Asian Pac J Cancer Prev, 13, 3-9.
- Farhath S, Vijaya P, Mumtaj P (2013). Cervical cancer: Is vaccination necessary in India? Asian Pac J Cancer Prev, 14, 2681-4. https://doi.org/10.7314/APJCP.2013.14.4.2681
- Govan VA (2005). Strategies for human papillomavirus therapeutic vaccines and other therapies based on the E6 and E7 oncogenes. Ann N Y Acad Sci, 1056, 328-43. https://doi.org/10.1196/annals.1352.016
- Ham S, Kim KH, Kwon TH, et al (2014). Luteolin induces intrinsic apoptosis via inhibition of E6/E7 oncogenes and activation of extrinsic and intrinsic signaling pathways in HPV-18-associated cells. Oncol Rep, 31, 2683-91.
- Li Q, Zhou ZX, Sheng W, Zeng Y (2013). HPV18 carcinogenic mechanisms and vaccine research. Modern Prev Med, 49, 1140-2.
- Mcintyre MC, Frattini MG, Grossman SR et al (1993). Human papillomavirus type 18 E7 protein requires intact Cys-X-X-Cys motifs for zinc binding, dimerization, and transformation but not for Rb binding. J Virol , 67, 3142-50.
- Narisawa-Saito M, Kiyono T (2007). Basic mechanisms of highrisk human papillomavirus-induced carcinogenesis: roles of E6 and E7 proteins. Cancer Sci, 98, 1505-11. https://doi.org/10.1111/j.1349-7006.2007.00546.x
- Nelson EA, Lam HS, Choi KC, et al (2013). Ho WC, Fung LW, Cheng FW, Sung RY, Royals M, Chan PK. A pilot randomized study to assess immunogenicity, reactogenicity, safety and tolerability of two human papillomavirus vaccines administered intramuscularly and intradermally to females aged 18-26 years. Vaccine, 31, 3452-60. https://doi.org/10.1016/j.vaccine.2013.06.034
- Ohlschlager P, Quetting M, Alvarez G, et al (2009). Enhancement of immunogenicity of a therapeutic cervical cancer DNAbased vaccine by co-application of sequenceoptimized genetic adjuvants. Int J Cancer, 125, 189-98. https://doi.org/10.1002/ijc.24333
- Pang CL, Thierry F (2013). Human papillomavirus proteins as prospective therapeutic targets. Microb Pathog, 58, 55-65. https://doi.org/10.1016/j.micpath.2012.11.002
- Powell N, Cuschieri K, Cubie H, et al (2013). Cervical cancers associated with human papillomavirus types 16, 18 and 45 are diagnosed in younger women than cancers associated with other types: a cross-sectional observational study in Wales and Scotland (UK). J Clin Virol, 58, 571-4. https://doi.org/10.1016/j.jcv.2013.08.020
- Siriaunkgul S, Utaipat U, Suwiwat S, et al (2012). Prognostic value of HPV18 DNA viral load in patients with early-stage neuroendocrine carcinoma of the uterine cervix. Asian Pac J Cancer Prev, 13, 3281-5. https://doi.org/10.7314/APJCP.2012.13.7.3281
- Xie Q, Zhou ZX, Li Z, et al (2011). Transforming activity of a novel mutant of HPV16 E6E7 fusion gene. Virologica Sinica, 26, 206-13. https://doi.org/10.1007/s12250-011-3178-9
- Immunotherapeutic Effects of Dendritic Cells Pulsed with a Coden-optimized HPV 16 E6 and E7 Fusion Gene in Vivo and in Vitro vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.3843